Dertinger Stephen D, Tsai Ying, Nowak Irena, Hyrien Ollivier, Sun Hongliang, Bemis Jeffrey C, Torous Dorothea K, Keng Peter, Palis James, Chen Yuhchyau
Litron Laboratories, Rochester, NY 14623, USA.
Mutat Res. 2007 Dec 1;634(1-2):119-25. doi: 10.1016/j.mrgentox.2007.06.010. Epub 2007 Jul 5.
A flow cytometric, anti-CD71-based method was used to measure peripheral blood reticulocyte and micronucleated reticulocyte frequencies in response to (137)Cs total body irradiation (TBI). In three independent experiments, groups of five female C57BL/6N mice were irradiated at graded doses up to 3 Gy, and peripheral blood specimens were collected at 43 h post-irradiation. Whereas the frequency of reticulocytes declined over the range of doses studied, micronucleated reticulocyte incidence was observed to increase in a dose-dependent manner up to 1 Gy. At doses greater than approximately 1 Gy, micronucleated reticulocyte frequencies declined with increasing exposure. These responses were highly reproducible, with significant effects on reticulocyte and micronucleated reticulocyte frequencies observed for the lowest dose studied (0.125 Gy). A time-course experiment was performed to test whether radiation-induced cell cycle delay may explain saturation of the micronucleated reticulocyte endpoint at doses >1 Gy. For this experiment, groups of four female C57BL/6N mice were exposed to 1, 1.5, or 2 Gy TBI, and blood collection occurred at 12h intervals from 43 to 115 h post-exposure. Reduced reticulocyte frequencies were observed for each dose studied, and the recovery of reticulocytes was increasingly delayed with higher radiation doses. Maximal micronucleated reticulocyte frequencies were observed at 43 or 55 h, with progressively lower values at later time points. At no time did micronucleated reticulocyte frequencies induced by 1.5 or 2 Gy significantly exceed that observed for 1 Gy at 43 h. These time-course data suggest that radiation-induced cell cycle delay cannot account for the micronucleated reticulocyte downturn phenomenon observed at doses greater than 1 Gy. An alternate hypothesis is discussed whereby apoptotic elimination of severely damaged bone marrow erythroid precursors plays a dominant role in saturating the radiation-induced micronucleated reticulocyte response observed for C57BL/6N mice.
采用基于抗CD71的流式细胞术方法，测量全身受¹³⁷Cs照射（TBI）后外周血网织红细胞和微核网织红细胞的频率。在三个独立实验中，将每组五只雌性C57BL/6N小鼠按高达3 Gy的梯度剂量进行照射，并在照射后43小时采集外周血样本。在所研究的剂量范围内，网织红细胞频率下降，而微核网织红细胞发生率在剂量高达1 Gy时呈剂量依赖性增加。在剂量大于约1 Gy时，微核网织红细胞频率随照射剂量增加而下降。这些反应具有高度可重复性，在所研究的最低剂量（0.125 Gy）下，网织红细胞和微核网织红细胞频率有显著变化。进行了一项时间进程实验，以测试辐射诱导的细胞周期延迟是否可以解释在剂量>1 Gy时微核网织红细胞终点的饱和现象。在该实验中，将每组四只雌性C57BL/6N小鼠暴露于1、1.5或2 Gy的TBI，并在暴露后43至115小时每隔12小时采集血液。在所研究的每个剂量下均观察到网织红细胞频率降低，且辐射剂量越高，网织红细胞的恢复延迟越明显。在43或55小时观察到微核网织红细胞频率最高，在随后的时间点值逐渐降低。在任何时候，1.5或2 Gy诱导的微核网织红细胞频率均未显著超过43小时时1 Gy所观察到的值。这些时间进程数据表明，辐射诱导的细胞周期延迟不能解释在剂量大于1 Gy时观察到的微核网织红细胞下降现象。文中讨论了另一种假设，即严重受损的骨髓红系前体细胞的凋亡消除在使C57BL/6N小鼠观察到的辐射诱导的微核网织红细胞反应饱和中起主导作用。
